SAMPL6 host-guest challenge: binding free energies via a multistep approach

Journal of Computer-aided Molecular Design
Yiğitcan EkenAngela K Wilson

Abstract

In this effort in the SAMPL6 host-guest binding challenge, a combination of molecular dynamics and quantum mechanical methods were used to blindly predict the host-guest binding free energies of a series of cucurbit[8]uril (CB8), octa-acid (OA), and tetramethyl octa-acid (TEMOA) hosts bound to various guest molecules in aqueous solution. Poses for host-guest systems were generated via molecular dynamics (MD) simulations and clustering analyses. The binding free energies for the structures obtained via cluster analyses of MD trajectories were calculated using the MMPBSA method and density functional theory (DFT) with the inclusion of Grimme's dispersion correction, an implicit solvation model to model the aqueous solution, and the resolution-of-the-identity (RI) approximation (MMPBSA, RI-B3PW91-D3, and RI-B3PW91, respectively). Among these three methods tested, the results for OA and TEMOA systems showed MMPBSA and RI-B3PW91-D3 methods can be used to qualitatively rank binding energies of small molecules with an overbinding by 7 and 37 kcal/mol respectively, and RI-B3PW91 gave the poorest quality results, indicating the importance of dispersion correction for the binding free energy calculations. Due to the complexity of the CB8...Continue Reading

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Citations

Nov 12, 2018·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Jan 28, 2020·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Jan 25, 2020·Journal of Computer-aided Molecular Design·Zhaoxi SunZhengdan Zhu
Oct 11, 2020·Journal of Computer-aided Molecular Design·Zhe HuaiZhaoxi Sun
Nov 6, 2020·Journal of Computer-aided Molecular Design·Yiğitcan EkenAngela K Wilson
Apr 4, 2021·International Journal of Molecular Sciences·Esra Boz, Matthias Stein
Nov 25, 2020·Environmental Science & Technology·Thanh T LaiAngela K Wilson
Feb 29, 2020·Journal of Chemical Theory and Computation·Yasser B Ruiz-Blanco, Elsa Sanchez-Garcia
Nov 25, 2021·Journal of Chemical Information and Modeling·Zhaoxi SunZhirong Liu

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